This is a single-center, randomized, open-label, single-dose, parallel-group study which will enroll and randomize approximately 48 subjects (to achieve 36 completers) with opioid use disorder (OUD) who are seeking treatment for OUD. The study includes both a Residential (Inpatient) and Non-Residential (Outpatient) Period.

Inclusion Criteria:

• Currently meets DSM-5 criteria for moderate or severe opioid use disorder (OUD)
• Is seeking treatment for OUD
• Body mass index: ≥ 18.0 to ≤ 35.0 kg/m^2
• Females: Female individuals of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative serum pregnancy test prior to enrollment and must agree to use a medically acceptable means of contraception from Screening through at least 6 months after the last dose of Investigational Medicinal Product (IMP).
• Males: Male individuals with female partners of child-bearing potential must agree to use medically acceptable contraception after signing the informed consent form through at least 6 months after the last dose of IMP. Male individuals must also agree not to donate sperm during the study and for 6 months after receiving the last dose of IMP.
• Have a normal electrocardiogram (ECG) or ECG with no clinically significant findings in the opinion of the Investigator or medically qualified sub-investigator at Screening and through pre-dose on Day 1.
• Agree not to take any buprenorphine-containing products, other than those administered for the current study, throughout the duration of the study.
• Willing to adhere to study procedures and provide written informed consent prior to start of any study procedures.

Exclusion Criteria:

• Current diagnosis, other than OUD, requiring chronic opioid treatment.
• Pregnant or lactating females.
• Have an ECG demonstrating a corrected QT interval using Fridericia's calculation (QTcF) > 450 msec in males and QTcF > 470 msec in females upon admission to the residential facility or prior to administration of RBP-6000.
• Currently meet the criteria for diagnosis of moderate or severe substance use disorder, by DSM-5 criteria, for any substances other than opioids, and/or tobacco.
• Had a significant traumatic injury, major surgery, or open biopsy within the 4 weeks prior to signing the informed consent form.
• Used buprenorphine-containing products within the 14 days prior to signing the informed consent form.
• Have a history of suicidal ideation within the 30 days prior to signing the informed consent form or prior to study drug administration
• Have a history or presence of allergic or adverse response (including rash or anaphylaxis) to buprenorphine, naloxone, methadone, or the ATRIGEL Delivery System.
• Individuals who have a positive urine drug screen (UDS) prior to admission to the residential facility for barbiturates, benzodiazepines, buprenorphine, or methadone.